Processing speed is among the most impaired neuropsychological domains in schizophrenia and is strongly associated with multiple dimensions of functional outcome, including self-care management and employment. Developing effective treatments for processing speed may improve functional outcome and reduce illness burden. Unfortunately, commonly used clinical neuropsychological tests lack the precision to delineate and measure specific cognitive mechanisms contributing to processing speed impairment. This has hampered efforts to understand the neural basis of processing speed dysfunction and is a significant barrier to the development of pro-cognitive interventions. This proposal seeks to address these barriers by using cognitive neuroscience-based tasks, namely single and dual-task choice reaction time (RT) experiments, to investigate processing speed impairment in schizophrenia. Cognitive models derived from these tasks posit that information processing speed is comprised of 3 stages: perceptual analysis, response selection, and response production. The available evidence from the handful of studies employing these paradigms suggests that response selection is differentially impaired in schizophrenia. However, it is not known if the impairment results from dysfunction of a unitary response selection process that cuts across sensory and motor modalities, or is modality specific. Resolving this issue is crucial to understanding the neural basis and treatment of the deficit. Generalized impairment would implicate dysfunction of a central, amodal response selection network and indicate that training programs shown to improve response selection and the speed of neural processing in amodal response selection brain regions should be attempted in schizophrenia. Conversely, modality-specific impairment would implicate dysfunction of modality-specific neural machinery and suggest that interventions targeting specific sensory and/or motor processes might be more effective at improving processing speed in schizophrenia. Evidence that auditory training improves verbal learning and memory provides a striking demonstration of a modality-specific approach to improving cognition in schizophrenia. The specific aims of this proposal are: 1) test the hypothesis that response selection impairment in schizophrenia generalizes across sensory and motor modalities; and 2) examine the integrity of multi-modal response selection brain networks and modality-specific brain regions in schizophrenia. The anticipated results of this work will further our understanding of the specific cognitive operations contributing to slowed processing speed in schizophrenia, identify candidate biomarkers of processing speed dysfunction, and lend guidance to the development and selection of pro-cognitive interventions. PUBLIC HEALTH RELEVANCE: Cognitive impairment in schizophrenia leads to profound disability and is a robust predictor of multiple dimensions of outcome, including self-care management, social functioning, and employment. This proposal will use cognitive neuroscience based methods to better understand the nature and neural basis of cognitive impairment in schizophrenia. The results of this work will help guide the selection of existing therapies to improving cognition and facilitate the development of novel pharmacological and non-pharmacological pro-cognitive interventions.